Prostate gland development is dependent on stromal-epithelial interactions. Urogenital sinus mesenchymal cells induce and direct epithelial proliferation and differentiation in a tissue-specific manner. Specific mechanisms are unknown. Benign prostatic hyperplasia is a disease typified by stromal and accompanied glandular hyperplasia. Stromal factors involved in processes of epithelial growth and differentiation control are likely involved in this disease. The previous project period focused on the identification and characterization of the protein exhibiting UGIF activity. Studies to date have reported the purification of the ps20 (UGIF) protein, amino acid sequence analysis, biological activity, development of antibody probes, immunohistochemical localization, and the cloning of full length cDNA encoding ps20. Cloning and nucleotide sequence analysis indicated ps20 is a novel member of an existing protein family. Predominant members exhibit tissue modeling functions in development. It is our hypothesis that ps20 is fundamental to mechanisms of stromal-epithelial interactions in development and adult tissue, is involved in alterations of prostate proliferative diseases, and is likely a new marker for the study of smooth muscle ontogeny. To address these hypotheses and fundamental mechanisms of action, we propose: To determine spatial, temporal, and hormone-regulated patterns of ps20 expression in embryonic development, in postnatal and adult rat prostate gland; To prepare and characterize biologically active and inactive recombinant ps20; To determine ps20 target cell types and characterize mediation of ps20 activity through membrane-bound and/or secreted proteins and; To identify ps20-interactive proteins. The proposed studies are required to focus long term approaches. It is anticipated that a more complete hypotheses regarding ps20 mechanisms of action will be generated from these studies.